PROJECT SUMMARY The growing prevalence of antibiotic resistance is a threat to human health globally. More than 80% of the world?s population lives in low- and middle-income countries that are particularly challenged by antibiotic resistance. This situation arises because of greater disease burdens, greater antibiotic demand, greater unsupervised antibiotic availability, and more opportunities for transmission of pathogens and antibiotic-resistant bacteria that, in turn, increases disease incidence and demand for antibiotics. We hypothesize that the transmission component of this process is even more important than antibiotic use, and consequently interventions that limit transmission would be most efficacious in resource-limited settings. The proposed project will directly assess the connection between burden of disease (defined as syndromic illness including acute febrile illness, diarrhea, and respiratory infections) and subsequent demand for antibiotics on the prevalence of antibiotic-resistant bacteria (commensal and pathogenic). We will establish a surveillance platform in a rural and an urban community located in the Quetzaltenango Department of Guatemala. A cross-sectional, randomly-selected sample of households (n=600) will be enrolled during the initial phase of the study, and both stool and throat samples will be collected to detect the presence (colonization) of extended-spectrum cephalosporin-resistant Enterobacteriaceae (ESCrE), carbapenem-resistant Enterobacteriaceae (CRE) and Group A Streptococcus. The baseline data will be compared with subsequent longitudinal samples while cases of syndromic illness will be investigated at the enrolled households. Pathogen isolation and tracking of patients at local hospital will be used to examine the healthcare contribution to the prevalence of antibiotic resistance in the community. If funding is available, the surveillance platform will continue to collect baseline prevalence data on antibiotic resistance and investigate syndromic illness for three years. Additional work will include molecular characterization of bacterial isolates and inclusion of a separate cross- sectional study to examine the prevalence of antibiotic-resistant bacteria in a community that has a higher incidence of acute febrile illness. Data from years 1-3 will be used to identify and test interventions during years 4-5.